The cloning of frogs from somatic cells demonstrated that differentiation from the zygote into specialized cell types was a reversible process. The transplantation of somatic nuclei into unfertilized mammalian oocytes resulted in the cloning of sheep, mice, cows and various other mammalian species.
The derivation of embryonic stem cells from human blastocysts brought the prospect of combining nuclear transfer and stem cell derivation to generate cells and tissues for patients requiring replacement of diseased cells or tissue. This concept was realized in the mouse for the correction of immunodeficiency and of Parkinson's disease (Rideout et al. 2002 Cell 109(1): 17-27). Nuclear transfer stem cells were also derived from the rhesus monkey (Byrne et al., 2007 Nature 450 (7169): 497-502). However, these techniques have previously not been accomplished in human cells, possibly because of species-specific differences.
To date, no methods are known for the derivation of a human embryonic stem cell line after nuclear transfer, although nuclear transfer embryos have been generated which have developed to the cleavage stages. Human embryos generated by conventional nuclear transfer methods consistently arrest at the late cleavage stages with karyotypic and transcriptional defects, prohibiting stem cell derivation. Thus, there remains a longstanding need in the art for a method for the nuclear transfer of human cells, combined with the derivation of embryonic stem cells.